(2) HIV Clinical Manifestations Flashcards
What is the primary HIV infection?
Acute Retroviral syndrome - HIV infection PRIOR to seroconversion
How does acute retroviral syndrome present?
o Fever o Sweats o Malaise o Myalgias o Anorexia o Nausea o Diarrhea o Non-exudative pharyngitis
When does Acute Retroviral Syndrome occur?
- Onset 1-6 weeks from exposure – peaks at 3 weeks
* Symptoms generally resolve in 10-15 days
What is the window period?
= patient infected but antibodies not yet detected- they have a high viral load, very infectious to others, but cant detect HIV on an ELISA (remains negative for 2-6 weeks after onset of symptoms)
How does the Lab evaluate ARS?
Detection of HIV specific antibodies in plasma or serum : HIV antibodies = seroconversion
• Appear a few weeks after infection o 5% within 7 days o 50% within 20 days o 95% within 90 days why we test after 4 weeks, 3 months
What are the laboratory characteristics to look for in someone with suspected HIV?
Reduced total lymphocyte count (lymphopenia followed by lymphocytosis from expanded CD8 cells).
CD4 count plummets (CD4:CD8 ratio is inverted)
HIV p24 antigen - detected in 75% of people in serum or CSF within 2 weeks of exposure
HIV RNA markedly elevated in most patients
ELISA for HIV antibodies remains negative for 2-6 weeks after onset of symptoms
Anti-p24 appears on the western blot first
What is the standard screening test for HIV?
ELISA
HIV antigens exposed to & bound by HIV antibodies in serum
Presence detected by second anti-human antibody
HIV 1&2 in most commercial kits
->+ve in 3-6 weeks
When can you get a false positive ELISA?
Recent immunisation (HBV, Influenza) Autoimmune disease Pregnancy (due to antibodies to HLA antigens) Multiple myeloma End stage renal failure
When can you get false negative ELISA
WIndow period
- acute infection prior to antibody development
- HIV-2 N or 0 group infections
- Hypogammaglobulinemia
When do you do a western blot?
TO confirm a positive ELISA
What does a Western blot show?
Detects antibodies in patients sera that react with a number of different viral proteins ->Uses gel electrophoresis to detect proteins
HIV proteins are first separated by electrophoresis, Then blotted onto nitrocellulose membrane, The membrane is incubated with patients serum ->Specific antibodies fix to the respective HIV proteins ->Produces coloured band after colouring reaction
Distinct bands of different molecular weight using protein gel electrophoresis
Positive if all 3 groups:
- > Gag p24 (usually first)
- > Envelope proteins – gp160, gp120, gp41 (second)
- > Polymerase proteins – p66 or p51
What are the clinical symptoms of ARS?
• Often there is a maculopapular, diffuse rash – involves face, neck and trunk
o Can be misdiagnosed: meningococcal, drug reactions, viral infections
How do we treat ARS?
Reduce symptoms & transmission
ART recommended for all persons with HIV infection & should be offered to those with early HIV infection.
All pregnant women with early HIV infection should start ART as soon as possible to prevent perinatal transmission of HIV to baby ->is some concern re affect of ART on baby, but bad affects occur in first 5-6 weeks before they know they are pregnant
If treatment is initiated in a patient with early HIV infection, the goal is to suppress plasma HIV RNA to below detectable levels
For patients with early HIV infection in whom therapy is initiated, testing for plasma HIV RNA levels, CD4 count, and toxicity monitoring should be performed as described for patients with chronic HIV infection
What are some of the clinical manifestations of HIV?
Persistant generalised lymphadenopathy
Oral Disease(OHL, candida infection, gingovitis, peridonditis, oral ulcers, KS, non hodkins lymphoma)
VZV
What is PGL (Persistant generalised lymphadenopathy)
Pathogenesis
Definition
Seen in 75% of infected individuals
Pathogenesis: rapid infection of CD4 cell in lymph nodes by HIV after initial infection
Defined as presence of 2 or more sites of extra inguinal lymphadenopathy for a minimum of 3-6 months for which no other explanation can be found.
In HIV - usually symmetrical, 0.5-2cm, mobile and rubbery
What are the differentials you would want to discount in diagnosing someone with persistant generalised lymphadenopathy?
• Differentials – o Sarcoid o Secondary syphilis o Hodgkins lymphoma o Mycobacteria o KS o Lymphoma o Castleman’s disease (angioproliferative hyperplastic process of lymph nodes)
When would you see a candida infection (oral thrush)?
How would you treat it?
Differentiate as you can scrape these off
- white plaques over the hard and soft palates, buccal mucosa, tongue, pharynx and hypopharynx
- seen more commonly when CD4 falls below 200-300.
- Diagnosis often made by appearance alone.
- Often accompanied by candida oesophagitis = AIDS defining illness
- Treated with FLUCONAZOLE
When would you see Oral hairy leukoplakia?
What would you want to discount from your diagnosis?
Oral Hairy Leukoplakia (OHL) - Associated with EBV - Diagnosed o On visual inspection o Inability to scrape off o *Failure to respond to antifungals o And on biopsy • Treatment o Restoring the immune system
Other oral diseases
Severe gingivitis & periodontitis (foul smelling)
o Must be taken seriously – rapid gum loss
- Oral ulcers
- KS – blue/red papules in the back of the mouth
- NHL (non-hodgkins lymphoma)
When would you see VZV?
Treatment?
20-30x more common in patients with HIV
May cross between dermatomes in patients with HIV
• VZV much more common in patients with HIV (12-30%)
Disseminated zoster >10 cutaneous lesions
Treatment = Valaciclovir
In severe immunosuppression IV acyclovir may be preferred
o Infection control – keep isolated (if its just cutaneous – cover the lesion)
What happens to your CD4 count over the years?
CD4 – lose 50-70 cells per year
Advanced HIV more at risk of opportunistic infections (late stage disease CD4 <200)
Name some advanced infections which are AIDs defining:
Bacteria
- Mycobacterium avium complex
- Mycobacterium kansasii (disseminated/extrapulmonary)
- Mycobacterium tuberculosis
- Mycobacterium (other) – disseminated/extrapulmonary
- Salmonella (recurrent sepsis)
Name some advanced infections which are AIDs defining: FUNGAL
Candidiasis – bronchial, oesophageal, tracheal, pulmonary
Coccidioidomycosis – disseminated/extrapulmonary (America not Aus)
Cryptococcus – extrapulmonary
Histoplasmosis – disseminated/extrapulmonary
Pneumonitis jiroveci – pneumonia
Name some advanced infections which are AIDs defining: Protozoan
- Cryptosporidiosis (intestinal, >1 month)
- Isosporiasis (intestinal, >1 month)
- Toxoplasmosis (brain)
Name some advanced infections which are AIDs defining: Viral
- Cytomegalovirus (other than liver, spleen or nodes)
* Herpes simplex virus (chronic ulcers >1 month or oesophagitis, bronchitis, pneumonitis)
Name some advanced infections which are AIDs defining:Malignancies
- Cervical cancer (invasive)
- Kaposi’s sarcoma
- Lymphoma (Burkitt’s, immunoblastic, brain primary)
Name some advanced infections which are AIDs defining: OTHER
- Encephalopathy (HIV)
- Progressive multifocal leukoencephalopathy
- Pneumonia (≥2 episodes in 12/12)
- Wasting syndrome >10% LOW or fever or weakness >30 days
What defines ‘late stage HIV’?
- CD4 <200
* Susceptible to opportunistic infections
For differential diagnosis’ according to presentation of COUGH & pulmonary infiltrate + CD4 count check notes
check notes.
What is PJP?
Pneumocystis jirovecii is the most common opportunistic infection in persons with HIV infection.
Implicated cause of interstitial plasma cell pneumonia in immunosuppressed
Unicellular fungi deposits in alveoli
Infants natural host for the disease – colonized in first few months of life → acquired early in life
Reactivation causes intra-alveolar pneumonitis (life threatening)
If CD4 <200 cells/mm3
What are the clinical features of PJP?
o Subacute insidious onset 2-4 weeks o Band-like tightness around thorax o Dry cough (non productive) o Febrile o SOB
What investigations would you do in someone with PJP?
- > Low SaO2
- > Bilateral & often diffuse interstitial shadowing on CXR (often spares lower zones)
->Up to 20% of patients will have –ve CXR but can CT scan, which will confirm positive findings
o Elevated LDH
o CD4 <250
